The long term objective of the research proposed in this grant application is to provide the neural mechanisms that can be used to explain angina pectoris and silent ischemia associated with myocardial ischemia. The focus of the current set of experiments is to analyze the activity of specific spinal cord neurons that are involved with transmission of nociceptive information following myocardial ischemia. Two major goals will be addressed. The first goal deals with cervical spinothalamic tract cells that are excited by vagal, sympathetic and phrenic afferents. The identification of the upper cervical segments as a region that receives cardiopulmonary input represents a new area that has not been investigated. The second proposed goal is to determine how chemical stimulation of the heart and coronary artery occlusion affect the activity of cervical and thoracic spinothalamic tract cells via afferent nerves that connect the heart with the central nervous system. The techniques employed involve extracellular electrophysiological studies of spinothalamic tract cells that are located in the first to third cervical segments and first through fifth thoracic segments of the spinal cord of deeply anesthetized primates. Changes in cell activity will be determined for electrical, chemical (bradykinin, adenosine, prostaglandins, and serotonin), and mechanical (occlusion of coronary arteries) stimulation of afferents from the heat and to electrical, mechanical and thermal stimulation of somatic structures. Responses to these interventions will be recorded before and after cervical vagal cooling, spinal cord cooling, dorsal root transections or sympathetic afferent cooling and transections. This approach will be used to determine how sympathetic, vagal and phrenic afferents contribute to the responses of spinothalamic tract cells during activation of cardiac receptors. The larynx and trachea also will be stimulated to determine how extra-cardiac input may contribute to the responses of these cells. Data derived from this study will serve as an important basis for understanding pain associated with myocardial ischemia in humans. Understanding how visceral sensation is transmitted and controlled in the central nervous system also may provide answers for the large population of humans who experience silent myocardial ischemia and are at risk for sudden death.